1. Field of the Disclosure
The disclosure relates to apoptotically active peptides and the use thereof for the production of pharmaceuticals.
2. Related Technology
Apoptosis is a genetically encoded suicide program which under particular physiologic or pathologic conditions is induced in eucaryote cells. The induction of apoptosis has to be controlled extremely precisely since hyperactivity can lead to degenerative disorders. Reduced apoptosis induction, on the other hand, can contribute to tumor progression.
Various low-molecular inductors of apoptosis have already been described. A significant class are tumor cytostatica. In most of the cases, it is, however, not clear in which way these cytostatica or other substances can induce apoptosis.
Induction of apoptosis can for instance result via a series of so-called death receptors, i.e. receptors including a “Death Domain” (DD) such as CD95, TNF-RI, DR3, DR4 or DR5, which after binding of their ligands induce apoptosis signal ways. The CD95 receptor, for instance, interacts after binding of the CD95 ligand with the adapter protein FADD/MORT1 whereby “recruitment” and activation of the protease FLICE/CASpase-8 are induced at the DISC, the “Death Inducing Signaling Complex”. FADD and FLICE each include “Death Effector Domains” (DED). Induction of apopotsis from outside via these signal ways is possible for instance by the addition of cell poisons (cytotoxic substances), by irradiation, viruses, withdrawal of growth factors or mechanical cell injure. These possibilities of apoptosis induction, however, are accompanied by special disadvantages. Addition of cell poisons, such as cytostatica, or irradiation in case of cancer cells leads to resistance development and, moreover, to damage of normal cells in which, originally, no apoptosis was to be triggered.
In general, induction of apoptosis is suggested for instance for the treatment of cancer, for avoiding angio-genetic processes etc. While inductors have here been described they still have a series of disadvantages. Cytostatica for instance generate heavy side-effects.
However, pathologic states are being discussed as well, wherein apoptosis has negative effects and for the treatment of which apoptosis should be inhibited.
An example of such a disease is arteriosclerosis. In particular, the inventors were earlier able to show that particularly in the area of the arteriosclerotic plaques, apoptotic cells (particularly endothelial cells, smooth muscle cells) come up and that such coming up is amplified by disturbed flow conditions, i.e. is flow-dependent (Freyberg et al., BBRC, 286, 141 149, 2001). Furthermore, the inventors could show that substances inhibiting the binding of TSP-1 to IAP and/or αvβ3 can also inhibit flow-dependent apoptosis.
Further diseases discussed in connection with increased up-coming apoptosis are AIDS and Alzheimer's disease.
Also in wound healing, apoptosis of participating cells such as fibroblasts, muscle cells and endothelial cells, plays a significant role. Inhibition of apoptosis should, therefore have a favorable influence on wound healing.